Browse
Submit Data
Databases
API
Help

Dataset Information

8 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pharmacotherapeutic strategies for treating cocaine use disorder-what do we have to offer?

ABSTRACT:

Background

Cocaine use contines to be a significant public health problem world-wide. However, despite substantial research efforts, no pharmacotherapies are approved for the treatment of cocaine use disorder (CUD).

Argument

Studies have identified positive signals for a range of medications for treating CUD. These include long-acting amphetamine formulations, modafinil, topiramate, doxazosin and combined topiramate and mixed amphetamine salts extended-release (MAS-ER). However, valid conclusions about a medication's clinical efficacy require nuanced approaches that take into account behavioural phenotypes of the target population (frequency of use, co-abuse of cocaine and other substances, genetic subgroups, psychiatric comorbidity), variables related to the medication (dose, short-/long-acting formulations, titration speed, medication adherence) and other factors that may affect treatment outcomes. Meta-analyses frequently do not account for these co-varying factors, which contributes to a somewhat nihilistic view on pharmacotherapeutic options for CUD. In addition, the predominant focus on abstinence, which is difficult for most patients to achieve, may overshadow more nuanced therapeutic signals.

Conclusion

While there is an emphasis on finding new medications with novel mechanisms of action for treating CUD, currently available medications deserve further investigation based on the existing literature. Evaluating refined metrics of treatment success in well-defined subgroups of patients, and further exploring combination therapies and their synergy with behavioural/psychosocial interventions, are promising avenues to establishing effective therapies for CUD.

SUBMITTER: Brandt L

PROVIDER: S-EPMC7930140 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Immunotherapeutic strategies for treating opioid use disorder and overdose.

Project description:IntroductionDevelopment and implementation of effective treatments for opioid use disorder (OUD) and prevention of overdose are urgent public health needs. Though existing medications for OUD (MOUD) are effective, barriers to initiation and retention in treatment persist. Therefore, development of novel treatments, especially those may complement existing treatments, is needed.Areas coveredThis review provides an overview of vaccines for substance use disorders (SUD) and mechanisms underlying their function and efficacy. Next, we focus on existing preclinical and clinical trials of SUD vaccines. We focus briefly on related strategies before providing an expert opinion on prior, current, and future work on vaccines for OUD. We included published findings from preclinical and clinical trials found on PubMed and ScienceDirect as well as ongoing or initiated trials listed on ClinicalTrials.gov.Expert opinionThe present opioid overdose and OUD crises necessitate urgent development and implementation of effective treatments, especially those that offer protection from overdose and can serve as adjuvants to existing medications. Promising preclinical trial results paired with careful efforts to develop vaccines that account for prior SUD vaccine shortcomings offer hope for current and future clinical trials of opioid vaccines. Clinical advantages of opioid vaccines appear to outnumber disadvantages, which may result in improved treatment options.

| S-EPMC10035039 | biostudies-literature

Emotion regulation strategies in individuals with cocaine use disorder maintained on methadone.

Project description:Background and objectivesCognitive reappraisal (CR) and emotional suppression (ES), two emotion regulation strategies, are disrupted in other substance use disorders but have not been studied in cocaine dependence.MethodsMethadone-maintained individuals with cocaine dependence (N = 72) completed assessment of CR, ES, cocaine use, and psychiatric symptoms.ResultsCR scores were associated with lower depression scores (r = -.29, p = .01), but not with cocaine abstinence during 8 weeks of treatment (r = .12, p = .29).Conclusions and scientific significanceCR appeared relevant to cocaine-dependent individuals' depression, but was not associated with abstinence or treatment outcome. (Am J Addict 2016;25:529-532).

| S-EPMC5367621 | biostudies-literature

Cocaine and Marijuana Polysubstance Use and Cocaine Use Disorder: Investigating Mediated Effects through Patterns of Cocaine Use.

Project description:ObjectivesCocaine use is on the rise and it is comorbid with marijuana use. We examined the association between lifetime cocaine + marijuana polysubstance use (CM PSU) versus cocaine only and lifetime cocaine use disorder (CocUD) and examined the potential mediation by cocaine use patterns. Methods: A total of 2,968 lifetime cocaine users were identified from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Mediation analysis was utilized to examine cocaine use quantity, frequency, and duration as potential mediators in the association between CM PSU and CocUD. A parallel multiple mediator model and a structural equation model were used, respectively, to examine: (1) the individual contribution of cocaine use quantity, frequency, and duration, and (2) combined contribution as a set specified by a latent variable. Results: Cocaine users were divided into 2,782 (93.7%) CM polysubstance users and 186 (6.3%) cocaine only users. CM PSU was associated with decreased risk of CocUD, but after including the mediators, the association was no longer significant. Examined separately, only quantity was found to be a significant mediator over and above frequency and duration, while the latent variable with three cocaine use pattern indicators explained 56.6% of the total association between CM PSU and CocUD. Conclusions: Compared to cocaine only users, CM polysubstance users were less likely to use cocaine heavily; this lower intensity of cocaine use was in turn associated with decreased risk of CocUD. Future research is warranted to determine the nature of the association between CM PSU and reduced CocUD.

| S-EPMC7902454 | biostudies-literature

Novel HDL-directed pharmacotherapeutic strategies.

Project description:The burden of atherothrombotic cardiovascular disease remains high despite currently available optimum medical therapy. To address this substantial residual risk, the development of novel therapies that attempt to harness the atheroprotective functions of HDL is a major goal. These functions include the critical role of HDL in reverse cholesterol transport, and its anti-inflammatory, antithrombotic, and antioxidant activities. Discoveries in the past decade have shed light on the complex metabolic and antiatherosclerotic pathways of HDL. These insights have fueled the development of HDL-targeted drugs, which can be classified among four different therapeutic approaches: directly augmenting apolipoprotein A-I (apo A-I) levels, such as with apo A-I infusions and upregulators of endogenous apo A-I production; indirectly augmenting apo A-I and HDL-cholesterol levels, such as through inhibition of cholesteryl ester transfer protein or endothelial lipase, or through activation of the high-affinity niacin receptor GPR109A; mimicking the functionality of apo A-I with apo A-I mimetic peptides; and enhancing steps in the reverse cholesterol transport pathway, such as via activation of the liver X receptor or of lecithin-cholesterol acyltransferase.

| S-EPMC3315102 | biostudies-other

Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models

Project description:Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a significant public health crisis that exacts tremendous personal and financial costs on patients and society. Sharp increases in cocaine use drive the urgent need for better mechanistic insight into this chronic relapsing brain disorder that currently lacks effective treatment options. To investigate the transcriptomic changes involved, we conducted RNA sequencing on two striatal brain regions that are heavily implicated in CUD, the nucleus accumbens and caudate nucleus, from postmortem brains of subjects with CUD and matched control subjects. Weighted gene co-expression analyses identified CUD-specific gene networks enriched in ionotropic receptors and associated with lowered neuroinflammation, contrasting the proinflammatory responses found in opioid use disorder. Integration of comprehensive transcriptomic datasets from mouse cocaine self-administration models revealed evolutionarily conserved gene networks in CUD that implicate especially D1 medium spiny neurons as drivers of cocaine-induced plasticity.

2022-12-19 | GSE214267 | GEO

Reinforcer pathology in cocaine use disorder: Temporal window determines cocaine valuation.

Project description:AimsThe Experimental Medicine Approach offers a unique perspective to determine clinical behavior change by engaging a target underlying the cause of a disorder. The present work engaged a novel target of addiction, Reinforcer Pathology, in two studies to test changes in behavior among individuals with cocaine use disorder.MethodsIn Study 1, n = 44 participants engaged the temporal window with episodic future thinking (EFT), a positive prospection exercise. Changes in temporal view and cocaine valuation were tested using delay discounting and behavioral economic demand, respectively. Additionally, a computational model assessed the relative reliance on the near- and far-sighted systems during EFT. In Study 2, n = 71 engaged the temporal window with a negatively-valenced hurricane scenario to test the opposite effects on window length and cocaine valuation.ResultsResults demonstrated systematic and symmetrical engagement of the behavioral target. Study 1 robustly replicated previous work, wherein EFT lengthened the temporal window and decreased cocaine valuation. Moreover, EFT increased the weighting of the modeled far-sighted system, increasing the relative impact of long-term discounting decisions. Study 2 produced opposite outcomes, shortened temporal window and increased cocaine valuation.ConclusionsThis approximately equal and opposite reaction to the manipulations supports reinforcer pathology theory and implicates the temporal window over which rewards are valued as a target to be pushed and pulled to produce clinically meaningful behavior change. Using the Experimental Medicine Approach as a guide, future work should identify new potential interventions to engage reinforcer pathology and use the clinically relevant outcomes as a litmus test for mechanism.

| S-EPMC8282732 | biostudies-literature

Developing new pharmacotherapeutic approaches to treating sickle-cell disease.

Project description:Survival for patients with SCD has been prolonged by improvements in supportive care, including vaccinations, antibiotic prophylaxis, and overall medical management, including tra nsfusion. However, there remains only one approved, partially effective drug for sickle cell disease-hydroxyurea (hydroxycarbamide). The world desperately needs better ways of both treating and preventing the recurrent painful vaso-occlusive episodes pathognomonic of sickle cell disease as well as the end-organ damage that still leads inexorably to severely shortened life expectancies throughout the world. Based on accumulating knowledge about how the abnormal red blood cells of sickle cell disease cause the double scourge of acute painful episodes and progressive end-organ damage, both pharmaceutical enterprises and individual investigators are now pursuing multiple new avenues for treating sickle cell disease. As a result, many compounds are in active development, both in preclinical models as well as in phase I, II, and III clinical trials. These agents target many pathophysiologic processes thought to be critical in sickle cell disease, including the chemical and physical behavior of haemoglobin S, cell adhesion, coagulation pathways, platelet activation, inflammatory pathways, and upregulation of haemoglobin F expression. In addition, recent explorations of the genetic variations that predispose to certain types of sickle cell disease-related tissue injury, such as stroke or nephropathy, are expected to lead to identification of drugs targeting the pathways uncovered by such work. Thus, the next five to ten years holds a promise of new treatments for sickle cell disease.

| S-EPMC5418585 | biostudies-literature

Pharmacotherapeutic Strategies and New Targets in OCD.

Project description:Effective pharmacological and psychotherapeutic treatments are well established for obsessive-compulsive disorder (OCD). Serotonin reuptake inhibitors (SRIs) are first-line treatment and are of benefit to about half of patients. Augmentation of SRI treatment with low-dose neuroleptics is an evidence-based second-line strategy. Specialty psychotherapy is also used as both first-line and second-line treatment and can benefit many. However, a substantial number of patients do not respond to these treatments. New alternatives are urgently needed. This review summarizes evidence for these established pharmacotherapeutic strategies, and for others that have been investigated in refractory disease but are not supported by the same level of evidence. We focus on three neurotransmitter systems in the brain: serotonin, dopamine, and glutamate. We summarize evidence from genetic, neuroimaging, animal model, and other lines of investigation that probe these three systems in patients with OCD. We also review recent work on predictors of response to current treatments. While many studies suggest abnormalities that may provide insight into the pathophysiology of the disorder, most studies have been small, and non-replication of reported findings has been common. Nevertheless, the gradual accrual of evidence for neurotransmitter dysregulation may in time lead the way to new pharmacological strategies.

| S-EPMC8634155 | biostudies-literature

Baseline cocaine demand predicts contingency management treatment outcomes for cocaine-use disorder.

Project description:Cocaine use disorder (CUD) is a significant public health issue. Behavioral interventions such as contingency management (CM) have been demonstrated to be highly effective in promoting cocaine abstinence. However, identifying individual characteristics associated with cocaine relapse may help improve treatment outcomes. Cocaine demand is a behavioral economic measure that shares a scientific foundation with CM. In the current study, we assessed baseline cocaine demand using a hypothetical cocaine purchasing task. Participants (N = 58) consisted of treatment-seeking individuals with CUD. All participants received 1 month of CM treatment for cocaine abstinence, and treatment responders were defined as presenting 6 consecutive cocaine negative urine samples from thrice weekly clinic visits. Demand data were well described by the exponentiated demand model. Indices of demand (intensity of demand [Q₀], elasticity [α]) were significantly associated with recent (last 30 days) cocaine use. Importantly, linear regression revealed that CM treatment nonresponders presented significantly higher Q₀ (p = .025). Subsequent quantile regression analyses examining the relationship between CM treatment response and Q₀ revealed statistically reliable effects of being a nonresponder across 3 of the lower percentiles (i.e., 15, 25, and 30). Overall, these findings provide further support for the utility of exponentiated demand model. To our knowledge, this is the first study to demonstrate an association between baseline demand and contingency management response and systematically extend the findings of prior demand research to a novel drug class, cocaine. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

| S-EPMC6928450 | biostudies-literature

Detecting Small Vessel Pathology in Cocaine Use Disorder.

Project description:BackgroundCocaine use is associated with an increased risk of cerebrovascular accidents. Small vessel pathology has been linked to the risk of stroke in cocaine users, but can be challenging to detect on conventional magnetic resonance (MR) scans. Fluid-attenuated inversion recovery (FLAIR) scans permit better resolution of small vessel lesions.ObjectivesFLAIR scans are currently only acquired based on the subjective judgement of abnormalities on MR scans at face value. We sought to evaluate this practice and the added value of FLAIR scans for patients with cocaine use disorder (CUD), by comparing microbleeds detected by MR and FLAIR scans. We hypothesised that microbleeds are more pronounced in CUD patients, particularly so in participants who had been selected for a FLAIR scan by radiographers.MethodsSixty-four patients with CUD and 60 control participants underwent a brain scan. The MR of 20 CUD patients and 16 control participants showed indicators of cerebral infarction at face value and were followed up by a FLAIR scan. We determined the volume of microbleeds in both MR and FLAIR scans and examined associations with various risk factors.ResultsWhile MR lesion volumes were significantly increased in CUD patients, no significant differences in lesion volume were found in the subgroup of individuals who received a FLAIR.ConclusionThe current practice of subjectively evaluating MR scans as a basis for the follow-up FLAIR scans to detect vascular pathology may miss vulnerable individuals. Hence, FLAIR scans should be included as a routine part of research studies.

| S-EPMC8867820 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data